Abstract
Moderate to severe diarrhea caused by Shigella is a global health concern due to its substantial contribution to morbidity and mortality in children aged <5 years in low- and middle-income countries. Although antibiotic treatment can be effective, emerging antimicrobial resistance, limited access, and cost affirm the role of vaccines as the most attractive countermeasure. Controlled human infection models (CHIMs) represent a valuable tool for assessing vaccine efficacy and potentially accelerating licensure. Currently, immunological analysis during CHIM studies is customized based on vaccine type, regimen, and administration route. Additionally, differences in type of immunoassays and procedures used limit comparisons across studies. In November 2017, an expert working group reviewed Shigella CHIM studies performed to date and developed consensus guidelines on prioritization of immunoassays, specimens, and collection time points. Immunoassays were ranked into 3 tiers, with antibodies to Shigella lipopolysaccharide (LPS) being the highest priority. To facilitate comparisons across clinical studies, a second workshop was conducted in December 2017, which focused on the pathway toward a recognized enzyme-linked immunosorbent assay (ELISA) to determine serum immunoglobulin G titers against Shigella LPS. The consensus of the meeting was to establish a consortium of international institutions with expertise in Shigella immunology that would work with the National Institute for Biological Standards and Control to establish a harmonized ELISA, produce a reference sera, and identify a reliable source of Shigella LPS for global utilization. Herein we describe efforts toward establishing common procedures to advance Shigella vaccine development, support licensure, and ultimately facilitate vaccine deployment and uptake.
Highlights
Several institutions have been involved with assessment of immune responses in Controlled human infection models (CHIMs) and field efficacy studies
Additional notes/recommendations from the Bill & Melinda Gates Foundation consensus table: Patients can be discharged after 2 culture-negative stools Fecal IgA/IgG: baseline followed by 1 week after each intervention Serology: baseline followed by weekly collections Affinity/avidity: baseline as well as 7 and 28 days postvaccination and challenge Serum subclasses: baseline as well as 7 and 28 days postvaccination and challenge ALS: baseline as well as 7 days postvaccination and challenge Memory B cell: baseline as well as 28 days postvaccination and challenge T follicular helper (Tfh): baseline as well as 3 days postvaccination and challenge RNA transcriptomics: recommended to correspond with every blood collection day Immunology for Shigella CHIM
The overall objective of the 2 workshops organized by the Bill & Melinda Gates Foundation was to help advance second-generation O-antigen–based Shigella vaccines by establishing consensus in the field regarding specimen collection, prioritization of Shigella-specific immunoassays, and harmonization of procedures to evaluate serum IgG responses directed to Shigella LPS
Summary
Several institutions have been involved with assessment of immune responses in CHIMs and field efficacy studies.
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